Human T-cell lymphotropic virus (HTLV-I)-associated myelopathy (hereinafter to be also referred to as “HAM”) is a chronically progressive myelitis induced by infection with HTLV-I, a human retrovirus. Although this disease is not a fatal disease, once it is developed, progressive gait disorders (finally in a bedridden state), dysuria and the like are certainly induced, and ADL and QOL of patients in the daily life are markedly limited. Therefore, this disease was designated as an intractable neurologic disease by the Ministry of Health, Labour and Welfare in 2008, and an urgent establishment of the treatment method therefor is highly demanded.
As a main, conventional treatment method for HAM is an immunomodulatory therapy such as administration of adrenal cortex hormone or interferon-α. This is a symptomatic therapy targeting chronic myelitis caused by HAM, which aims to improve clinical symptoms by the effect of a medicament having an immunomodulatory action. However, the effect of such treatment is not satisfactory, and the treatment takes a long time. Therefore, various problems including emergence of side effects, medical cost problem and the like have been pointed out (non-patent document 1). While alleviation of the above-mentioned problems has been tried by controlling the dose and dosing period of adrenal cortex, hormone and interferon-α, additional administration of vitamin C and the like, and the like, the problems have not been solved as yet. As other immunomodulatory therapy, various attempts such as plasma exchange therapy (non-patent document 2) and the like have been made. However, they also have similar problems.
As an anti-HTLV-I therapy for HAM, a zidovudine+lamivudine therapy has been reported. In a recent case-control study, the effectiveness thereof was not verified (non-patent document 3). In addition, an anti-HTLV-I therapy with an HDAC inhibitor valproic acid has a large problem in that it transiently and markedly increases the amount of peripheral blood HTLV-I provirus, which is a maximum risk factor for the HAM pathology.
The formation of HAM pathology starts with the infiltration of HTLV-I infected cells, which have increased markedly in the peripheral blood, into the spinal cord. Therefore, removal of the HTLV-I infected cells themselves from the body is considered to be the causal therapy of the disease; however, the treatment method has not been established yet.
The manner of HTLV-I infection is not infection with free virus particles but enlargement of infection by cell-to-cell spread. Specifically, HTLV-I starts cell-to-cell spread by the binding of coat protein gp46 of HTLV-I to HSPG (Heparan sulfate proteoglycan), which is a receptor of the target cell. Therefore, one target of the causal therapy is to prevent the binding and inhibit the cell-to-cell spread of HTLV-I, thereby preventing spread of HTLV-I in the body.
In relation thereto, one of the present inventors and others have reported that heparin, which is one of polysaccharide sulfates, shows an HTLV-I infection inhibitory action in a vitro test, and is clinically effective for HAM patients in an in vivo test (non-patent documents 4 and 5). However, heparin therapy has not been practicalized since consecutive and daily intravenous administration by injection is necessary, and a safety problem exists since heparin has a strong anticoagulant action.
As mentioned above, a causal therapy of HAM that can be practicalized has not been found to date. Moreover, various medicaments used for conventional HAM treatments failed to show an improving effect particularly as regards movement disorders associated with HAM, which has posed a large problem on medical treatments.